Blood Flashcards
What are the physiological functions of blood?
Transportation medium:
- Blood gases
- Nutrients
- Metabolites
- Information
- Heat
- Defense mechanism
- Haemostasis
- Homeostasis
Give the total buffer capacity for a bicarbonate buffer
53%
Give the total buffer capacity for non bicarbonate buffer
47%
Haemostasis
Coagulation
Reactions after vessel injuries
Effect of blood on homeostasis
Promotes:
- Isovolemia
- Isotonia
- Isoionia
- Isohydria
What proportion of blood is water?
90%
Composition of blood
- Plasma
- RBCs
- WBCs
- Thrombocytes
Blood + Anticoagulation and Centrifugation →
Plasma (with fibrinogen) + Cellular elements
Blood + long resting period
Serum (no fibrinogen)
Blood clot (fibrin-web)
Hematocrit
- Diagnostic parameter
- Shows the proportion of corpuscular elements to the whole volume
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Average hematocrit value
40% or 0.4
Average hematocrit value for dogs
0.46
Average hematocrit value for hens
0.32
What does the hematocrit show us?
The veloicty of sedimentation corpuscular elements
Blood cell sedimentation rate for horses
60-70 mm/hour
Blood cell sedimentation rate for dogs
5-10 mm/hour
Blood cell sedimentation rate for swine
1-14 mm/hour
Blood cell sedimentation rate for hens
1-4 mm/hour
Blood cell sedimentation rate for ruminants
0-2 mm/hour
Blood cell sedimentation rate for human
3-10 mm/hour
pH of blood
7.35 - 7.45
pHvenous <pHarterial
Give the relative viscosity of:
- Total blood
- Plasma
- Water
- Total blood: 4 (max 5.6)
- Plasma: 2
- Water: 1
Give the density of plasma
1020 g/l
Give the density of total blood
1052 g/l
Give the density of blood cells
1090 g/l
Give the freezing point of blood
-0.56°C
Give the total osmotic pressure of blood
700 kPa
Give the colloidosmotic/oncotic pressure of blood
2.7-4kPa
Give the osmolarity of blood
300 mmol/l
Give the blood volume of the body
80 ml/bwt
Give the plasma volume of the body
45 ml/bwkg
Give the blood cell volume of the body
35 ml/bwkg
Formula to calculate blood volume
V = Vrbc / 0.9 x Ht
V = Vp / (1-0.9 x Ht)
- Vp = Plasma volume*
- Vrbc = blood cell volume*
- Ht = Hematocrit value*
1, 4 and 7 are examples of…
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Normocythaemia
2, 5 and 8 are examples of
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Polycythaemia
3, 6 and 9 are examples of…
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Olygocythaemia
Normocythaemic normovolaemia
Healthy blood volume
Polycythaemic normovolaemia
- Haemoconcentration
- Viscosity increases
- Increased load on heart
Olygocythaemic normovolaemia
- Haemodilution
- Blood gets diluted with concurrent normal volume
Normocythaemic hypovolaemia (Oligaemia)
- Blood cells and plasma loss together
- Blood loss
- Plasma replaced quickly
- Cells return slowly
Polycythaemic hypovolaemia
- Anhydraemia: Lack of water/thirst
- Haemoconcentration
Normocythaemic hypervolaemia
- Plethora (A large amount)
- Excess transfusion
- Permanent, exhausting physical work
Olygocythaemic hypervolaemia
- Hydraemia
- Intake of excess water
- Infusion (followed by haemodilution)
Factors affecting blood volume
- Body fat
- Body position
- Muscle work
- Climate
- Nutrition
- Age
- Pregnancy
- Changes in water supply
Give the size of blood cells in:
- Mammals
- Birds
- Mammals: 6x2 µm
- Birds: 12x7 µm
Mean number of RBCs in the body
5 x 1012/L
Mitochondria are not present in RBCs, true or false
True
Average lifetime of RBCs
Average: 120 days
Cattle, swine: 60 days
Birds: 30 days
Haemoglobin concentration of blood
- 120-180 g/l
- 1.5-2.5 mmol/l
Haemoglobin content in 1g of RBCs
0.35g
35% haemoglobin concentraion
MCHC
Mean corpuscular hemoglobin concentration
Approx 5mmol/l
Calculate MCHC
Hb/Ht
- Hb = Hemaglobin*
- Ht = Hematocrit*
MCH
Value
Mean corpsucular hemoglobin
0.45 fmol/pc
Calculate MCH
Hb/RBC
MCV
Mean corpuscular volume
80-100 femtoliter/pc
Calculate MCV
Ht/RBC
Hemolysis
Leakage or disruption of the blood cells
Can be:
- Hypoosmosis
- Hyperosmosis
Hypoosmosis
- Blood cells placed in hypotonic solution
- Water flows into cells
- Cells swell and disrupt
Hyperosmosis
- Blood dropped into hypertonic solution
- Water leaves the cells
- Cells shrink
Osmotic resistance
RBCs adapt and are therefore resistant to the significant changes of osmotic circumstances
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Give the minimal osmotic resistance of RBCs
70-120 mmol/l NaCl
haemolysis just starts
Give the maximum osmotic resistance of RBCs
50 - 90 mmol/l NaCl
all the cells haemolyse
Osmotic resistance of the RBC is attributed to…
- The characteristics of the RBC membrane
- Spectrin protein molecules
- Fixed in place by ankyrine
- Give a flexible feature ‘molecular springs’
- On the internal side of the membrane
- Spectrin protein molecules
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Which physical effects can cause membrane haemolysis?
- Freezing
- Dissolving
- Shaking
- Shocking
- Osmosis
Which chemical effects can cause membrane haemolysis?
- Acids
- Liposolvents (E.g Ether, Chloroform)
- Surface tension reducers (Bile salts)
Which toxins can cause membrane haemolysis?
- Bacterial toxins
- Snake toxins
- Plant toxins
Haemoglobin
- Pigment (protein)
- Colours the RBCs
- Transports blood gases
- Forms the blood’s buffer capacity
Give the molecular weight of Haemoglobin
65,000 Da
- 4 sub units*
- 120-180 g/lblood = 1.5 - 2.5 mmol/l*
Haem/Hem
- Ferro-protoporphyrine
- Porphyrine base with 4 coordination sites
- Only the bivalent iron atom can bind to oxygen reversibly
- (Oxygenation)
Methaemoglobin
- Oxygenated derivative
- Binds to oxygen irreversibly
- Returned to the haemoglobin in the:
- Methaemoglobin-reductase-NADPH-systen
Fe2+ prefixes
- HEM
- Ferro-
- Hemo-
Fe3+ prefixes
- Hemin
- Ferri-
- Hemi-
Globin
- Determines characteristics of oxygen binding
- Allows allosteric stimulation
- Binds to oxygen stronger after accepting the former one
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Describe the evolution of blood cell genetics
- Originally one genetic chain (until 500 million years ago)
- Became alpha and beta chains
- 120 million years ago, beta chain spit into gamma1 and gamma2
- Beta1, beta2 and the epsylong chains also appeared through mutation
Sickle-cell anaemia
- Single amino acid change
- The 6th position of the beta chain should contain alanine
- It contains glutamine instead
Give the known Asian vector of malaria
Iwi bird
The age effect on RBCs
- Hb-F has a smaller affinity to 2,3-DPG
- (From cell metabolism, allows oxygen transport from mother to fetus)
- When compared with Hb-A due to the amino acid sequence
Adult haemoglobin
Hb-A = 2 alpha chains + 2 beta chains
Foetal haemoglobin
Hb-F = 2 alpha chains + 2 gamma chains
Oxygen in RBCs
- Bind to Fe2+ (reversible)
- 1 haem binds to 1 O2
- 1.34mlO2/ Hb
- 160mlO2/l blood
- 16% Volume
Carbon dioxide in RBCs
- Carbamino-hemoglobin
- Responsible for 20% CO2 transport
- Hb-NH2 + CO2 → Hb-N-COOH
Peak absorbance wavelengths for:
- HbO2
- Hb
- HbO2: 540nm, 580nm
- Hb: 555nm
Haemoglobin composition: Fe2+
Deoxi-Hb
Haemoglobin composition: Fe2+ O2
Oxygenated-Hb
Haemoglobin composition: Fe2+ CO
CO-Hb
Haemoglobin composition: Fe3+
Hemiglobin (Methaemoglobin)
Haemoglobin composition: Fe3+ Cl
Hemin chloride
Compare the affinity of carbon monoxide to oxygen
Carbon monoxide has 200 times greater affinity than oxygen
Haemoglobin can be irreversibly oxidised by…
OH and Cl radicals
Haemoglobin can reversibly bind to…
Oxygen
Methaemoglobin/Hemiglobin can be reversed by which reducing agent?
Intravenous methylene blue injection
Give the two most important buffer bases in the blood
- Hb-
- HCO3-
Which acid-base pair ensures buffer action in the blood?
HHb/Hb-
What percentage of buffer capacity is provided by haemoglobin?
35%
Which is a better proton acceptor?
- Deoxygenated Hb
- Oxygenated Hb
Deoxygenated
Give the stages of the degradation of haemoglobin
(Not via phagocytosis)
- RBCs → sphaerocytes
- Sphaerocytes → Spleen + liver
- Spleen + Liver release Haemoglobin
- Haptoglobin binds haemoglobin in blood
- Haemopexin binds haemoglobin in plasma
Describe how phagocytes break down haemoglobin
Haemoglobin broken down into:
- Globin → Aminoacid (recirculated)
- HEM → Fe (recirculated)**
- HEM → protoporfirin-IX → Bilirubin (then enters blood)
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Name given to bilirubin when bound to Albumin
Bilirubin-I
What percentage of bilirubin-I is conjugated with Glucuronic acid?
80%
What percentage of bilirubin-I is conjugated with sulphate
20%
When bilirubin conjugates, it becomes…
Bilirubin-II
Where is Bilirubin-II deconjugated and how?
- In the gut
- Deconjugated by bacteria
Function of gut bacteria:
- Bilirubin-II →
- Bilirubin-I →
- Stercobilnogen
- Urobilinogen (UBG)
Give the fate of Stercobilnogen
- Oxidised
- Stercobilin formed
- This passes into the faeces (stercobilin makes it brown)
Give the fate of urobilinogen
- Absorbed by the gut
- Portal circulation → Liver (14%)
- (Converted back to bilirubin)
- Absorbed by vv. hemorriodhales (1%)
- Systemic circulation → Renal excretion (Urine)
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Bilirubin-II
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Bile
Containing bilirubin-II
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Bilirubin-I
after degredation by bacteria
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Stercobilinogen
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Stercobilin
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Urobilinogen (UBG)
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Urobilinogen (UBG)
In embryonic stages, the red marrow recieves its blood-forming function by…
The embryionic liver
(blood-forming function also given to the spleen in mice)
Blood cell types are derived from
Progenitor cells (after a maturation stage)
During embryonic stages, which primordial cell type doesn’t roam to the bone marrow?
T-progenitor cell
(settles in the thymus, produces T-lymphocyte)
Give the stages of blood cell development
- Omnipotent primordial cell
- Committed progenitor cell
- Burst forming cell, erythroid
- CFC-E colony
- Normoblasts
- Reticulocyte
- Erythrocyte
What can a reticulocyte number >0.5% be a clinical indicator of?
Forced blood synthesis
Describe nucleus expulsion during blood cell development
- MHC structures roam to the pole
- Nucleus and MHC structures are exocytosed
- Blood type-specific antigens remain on the RBC surface
- Reticulocyte forms inside (not fully mature RBC yet)
Hb-mRNA is left in the cell, haemoglobin synthesis continues in endoplasmic reticulum
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Give the factors affecting RBC synthesis
- Oxygen supply
- Hypoxia
- High altitude
- Blood loss
- Kidney status
- REF (renal erythropoietic factor)
- Age
Describe the spleen colony test
- X-rays halt hematopoesis in animal 1
- Bone marrow cells implanted from animal 2 to animal 1
- 2 weeks lapse, implanted RBCs appear in animal 1
- Spleen becomes enlarged, signal peptides increase in blood
Erythropoetin
- Size (in mouse)
- Producing cell
- Target Cell
- Size: 51,000 Da
- Producing cell: Kidney cells
- Target cell: CFU
(RBCs)
Interleukin-3 (IL-3)
- Size (in mouse)
- Producing cell
- Target Cell
- Size: 25,000 Da
- Producing cell: T-lymphocyte, epidermis
- Target Cell: CFU, progenitor and mature cells
Granulocyte/Macrophage SF (GM-SF)
- Size (in mouse)
- Producing cell
- Target Cell
- Size: 23,000
- Producing cell: T-lymphocyte, endothel, fibroblast
- Target cell: GM progenitor cells
Granulocyte CSF (G-CSF)
- Size (in mouse)
- Producing cell
- Target Cell
- Size: 25,000 Da
- Producing cell: Macrophage, fibroblast
- Target cell: GM progenitor and neutrophil
Macrophage CSF (M-CSF)
- Size (in mouse)
- Producing cell
- Target Cell
- Size: 70,000 Da
- Producing cell: Fibroblast, macrophage, endothel
- Target cell: GM progenitor and Macrophage
Steel factor
- Size (in mouse)
- Producing cell
- Target Cell
- Size: 40-50,000 Da
- Producing cell: Stroma of many organs
- Target cell: CFU
(RBCs)
White blood cells
- Develop in bone marrow, except lymphocytes
- Mammals: 5-15 x 109/Lblood
- Birds: 20-30 x 109/Lblood
- Dependent on: Age, sex, time of day
The pathological increase in the number of the white blood cells
Leukocytosis
Causes of leukocytosis
- Bacterial infection
- Viral infection
- Parasitic infection
- Inflammatory processes
Decrease of white blood cells
Leukopenia
Leukopenia can be caused by
- Radiation
- Mushroom toxins
- Medications
Neutrophyl, eosinophyl and basophyl are kinds of…
Granulocyte
Lymphocyte and monocyte are types of…
Agranulocyte
Neutrophil is …% neutrophylic
60%
Lymphocyte is …% lymphocytic
60%
Neutrophylic WBCs are found in…
Horses, carnivores, humans
Lymphocytic WBCs are found in…
Ruminants, swine, birds
Neutrophil granulocyte
- 10-14µm
- Segmented nucleus
- Lysosomes present
- Previous meeting of pathogens not necessary for elimination
Lifetime of neutrophil granulocytes
Circulation: 6-7 hours
Tissue: 2-3 days
Where are Neutrophil granulocytes produced?
What is the mobilisation of these called?
- Bone marrow
- Spleen
Mobilised during Leukocytosis
What are the % compositions of granules in the Neutrophil granulocyte
- 80% neutrophil
- 20% azurophil
List the enzymes of granules in a Neutrophil granulocyte
- Lysosyme
- Nuclease
- Protease
- Myeloperoxidase
- Superoxid dismutase
- Acidic/alkalic phosphatase
Describe the adhesion of white blood cells
WBCs adhere to the wall of capillaries
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Describe the final developmental stages of the neutrophil granulocytes
- Young cells - Stick-shaped nucleus
- Becomes more segmented
- Stick shape increases with infection rate
- Granulocytopenia in decreased development
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What are the developmental stages of neutrophil granulocytes
- Young forms
- Stick shape
- Bean form
- Matured neutrophil (3-5 segmented nucleus)
- Over matured neutrophil (5-10 segmented nucleus)
What is the ‘shift to the left’ in blood count?
- Forced hematopoiesis
- Presence of fresh (acute) infection
What is the ‘shift to the right’ in blood count?
- Presence of aged neutrophil granulocytes
- Incomplete hematopoiesis
Neutrophil granulocyte migration is based on
Actin bundles:
- Contractile
- Gel-forming
- Tightly united
Describe Diapedesis of Neutrophil granulocyte
- Granulocyte phyllopodium adheres between capillary enothelial cells
- Granulocyte moves between the endothelial cells
- Cell moves into the interstitial space
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A complex consisting of three small and three bigger peptides
Clathrin
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Ligand
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Lysosome
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Surface receptor
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Nucleus
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Actin cortex
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LDL receptors ‘recruited’ by chlaritin
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Chlaritin complex
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Individual LDL receptor
Describe the diagram
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- Actin directed border forming
- Ligand binding
- Actin dependent forming of pseudopodia
Describe the figure
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- Internalisation
- Assisted with actin and fusogenic proteins
- Actin-binding
- Synthesis of fusogenic proteins
Describe the figure
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Phagosome synthesis
Describe the figure
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Phago-lysosome synthesis
Describe the figure
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- Residual body synthesis
- Oxidative ‘burst’
- Digestion
Give the stages of the respiratory burst
- First enzymatic step: NADPH-oxidase
- Second enzymatic step: SOD
- Third enzymatic step: MPO
Give the reaction of the first enzymatic step of phagocytosis
- NADPH-oxidase
- NADPH + 2O2 = 2O• + NADP + H+
- Active oxygen radical
Give the reaction of the second enzymatic step of phagocytosis
- SOD
- Superoxide dismutase
- 2O• + H2O → 2H2O2
Give the reaction of the third enzymatic step of phagocytosis
- MPO
- Myeloperoxidase
- H2O2 + Cl- → ClO- + H2O
- The most aggressive
Phagocyting ability increases …. times higher in the presence of a foreign body
100 times
Opsonisation
Where natural substances in the plasma e.g C3b factor can bind foreign antigen bodies to the receptor of a granulocyte.
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Immune adherence
Similar to opsonisation only with the presence of an antibody/immunoglobulin
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Basophil granulocyte
- Rarest WBC type
- Mast cells found in tissues
- Limited movement
-
Loosen tissues in the presence of antigens
- Allows other defence elements to move to the place of infection
- Act as a stimulent of antigen elimination
Name the enzymes present in Basophil granulocytes
- Hyaluronidase (specific)
- Protease
- Myeloperoxidase
Degranulation
- Stimulated in different ways
- The release of granules (and therefore enzymes)
- The enzymes loosen the environment
- Extreme degranulation: pathological damage in the animal’s own tissues - allergy
Give the specific degranulation pathway
- Antibodies are forming, slower reaction
- Antigen + antibody/complement stimulates degranulation
- Normal response: Tissues loosen, immune cells access tissues
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Give the non-specific degranulation pathway
- Complememnts are always present, quick reaction
- Antigen + antibody/complement stimulates degranulation
- Pathological response: Anaphylaxis
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What is a cytophilic antibody?
- An antibody that attaches to the basophil granulocyte
- The granulocyte has already prepared binding for antigens due to the antibody acting as a compliment
Which contents of the basophil granulocyte granules cause the tissues to loosen
- Histamine
- Heparin
- Hyaluronidase
What causes anaphylaxis?
- Degranulation
- Heparin release
- Accelerates antibodies entering the interstitium
- Accelerates Slow-reacting factor of anaphylaxis
- Causes long lasting inflammation
What does heparin help to prevent?
Coagulation
Eosinophil granulocyte
- Contains ‘granules’ in the form of lysosomes
- Lifetime: 3-5 days
- Has an antiallergic effect
- Proportion increases during allergic processes
- Pinocytosis only
- Cellular elimination in parasites
Give the enzymes contained in the Eosinophil granulocyte
- Histaminase
- Aril-sulphatase
- Myeloperoxidase
- Acidic and alcalic phosphatase
- Nuclease
During Chemotaxis, WBCs migrate towards which specific signals?
- Products of tissue breakdown
- Histamine
- Complement factors
- Chemotaxines produced by WBCs
Describe the antiallergic effect of Eosinophil granulocytes
- Basophil/Mast cell releases histamine and SRS-A
- Histamine and SRS-A enter eosinophil via pinocytosis
- Histaminase breaks down histamine
- Aryl-sulphatase breaks down SRS-A
SRS-A
Slow reacting substance of anaphylaxis
Mononuclear phagocytes
- Contain Azurophyl granules (lysosomes)
- Produces intracellular and extracellular enzymes
- MPS: Mononuclear phagocyte system
- MS: Macrophage system - antigen presentation, secretion
- RES: Reticulo endothelial system
- RHS: Reticulo hisiocytic system
- Lifetime: 2-3 months in tissue
Polynuclear giant cells
Polynuclear phagocytes with dividing capacity
Increased phagocytosis
Describe the migration and chemotaxis of mononuclear phagocytes
Similar to neutrophil granulocytes
Circulating fraction is really small
Extravasal supply: tissue macrophages
Give the intracellular enzymes of mononuclear phagocytes
- Proteases
- Myeloperoxidae
- Superoxid dismustase
- Acidic and alcalic phosphatase
Give the extracellular enzymes of mononuclear phagocytes
- Collagenase
- Elastase
- Angiotensine convertase
Give the macrophage cell of connective tissue
Histiocyte
Give the macrophage cell of liver
Kuppfer cells
Give the macrophage cell of the lung
Alveolar macrophage
Give the macrophage cell of lymphnodes
Fix and migrating macrophage
Give the macrophage cell of the spleen
Fix and migrating macrophage
Give the macrophage cell of bone marrow
Fix macrophage
Give the macrophage cell of pleura
Pleural macrophages
Give the macrophage cell of the peritoneum
Peritoneal macrophages
Give the macrophage cell of bone tissue
Osteoclasts
Give the macrophage cell of the nervous system
Microglia
Phagocytes not only demolish foreign bodies but…
The organism’s own perished and aged cells
Describe antigen presentation in a specialised APC (antigen presenting cell)
- Macrophage eliminates pathogen
- Digested pieces of antigen from the pathogen are kept
- Antigen expressed on macrophage surface protein
- MHC-complex II (Main histocompatibility complex)
- T-cell receptor recognises the antigen fragment
- Immune system initiated
- Antibody production
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Describe antigen presentation in an infected somatic cell
- Foreign material presented on cell surface
- Antigen presented on the MHC-I protein
- Cytotoxic T-lymphocyte recognises the MHC-I complex
- The infected cell is destroyed
Secretion of MPS (mononuclear phagocyte system) cells
Tissues are loosened by:
- Collagenase
- Elastase
- Angiotensine convertase
Immune response is stimulated by:
- Interleukin-1
- Interferon
- Prostaglandins
What is the effect of interleukin-1 on B-lymphocytes
Antibody synthesis
What is the effect of interleukin-1 on T-lymphocytes
Interleukin-2 synthesis
What is the effect of interleukin-1 on the hypothalamus
Production of fever
What is the effect of interleukin-1 on bone marrow
Neutrophil granulocyte production
What is the effect of interleukin-1 on fibroblasts
Collagen synthesis
What is the effect of interleukin-1 on the liver
Synthesis of acute phase proteins
Lymphocytes
- Agranulocyte
- Small, medium and big
- Small/middle sized: Found in circulating blood
- Large sized: Antigen specific lymphocyte subpopulations
- B-lymphocytes (small)
- T-lymphocytes (medium)
- Lifetime: Hour to years
- Antibody production
- No phagocytosis
T-lymphocytes
- Prouduced in thymus
- Responsible for cellular immunity
B-lymphocytes
- Site of production
- Function
- Bursa fabricii (bone marrow, embryonic liver and spleen)
- Humoral immunity
Where are lymphocytes found?
In all tissues except for:
- cornea
- heart valve
The decrease in lymphocytes in the blood
Lymphopaenia
The increase in lymphocytes in the blood
Lymphocytosis
Function of B-lymphocytes
Produces immunoglobulins
Function of T-lymphocytes
- Cellular immune response
- Stimulation of humoral immune response
Function of ‘0’ cells (NK cells)
Kills cells infected by tumour or virus
WBC development
- Pre-colony-forming-cells (multipotent) can reproduce in any direction (RBC/WBC producing)
- Direction committed and proliferable progenitor cells develop
- Maturation into final blood cell type
During embryonic life, which cell type doesn’t migrate to the bone marrow?
T-progenitor cell
Thrombocytes (Platelets)
- In birds, platelets can act as phagocytes
- 2-8x1011 pcs/L
- Lifetime: 5-10 days
- No nucleus
- Smallest blood cell
- Origin: Polycaryocyte giant cells (in red bone marrow)
Which types of granules are found in thrombocytes?
- Alpha-granules
- Store coagulation factors
- Delta-granules
- Store serotonin from the plasma
What prompts the release of granules from platelets?
Thrombocyte activating factors
Describe the morphology of the platelet
- Plasma membrane:
- wide glycocalix
- Cell adhesion molecules (CAM)
- Internal tubular system
- Peroxidase
- Prostaglandins
- Lysosomes: Acidic hydrolases
- Peroxisomes: Catalase
Function of the platelet actin cortex
- Shrinks clots
- Helps alpha granules vacate
Describe the function of the microtubular cortex
- During the activation of the system
- Cytoplasmic processes form on the platelet surface
- Increases retractions
- Increases efflux of coagulation factors
Describe blood groups
- Antigens that appear on the surface of blood cells
- Discovered by Karl Landsteiner
- 15 different types in humans
- Antibodies produced postnatally against non-posessed RBC antigens
- Non-posessed RBCs are agglutinated
How are blood groups used in veterinary medicine
- Parentage testing
- Prediction of certain production trait selection
- Prevention of certain illnesses
Why are blood transfusions in animals lest risky than in humans?
- There are only a few antibodies agains RBC antigens
- The antigens can be found in RBCs and plasma too
- __During transfusion: antibody is neutralised in plasma already
- RBC-dissolving capacity therefore diminishes
- __During transfusion: antibody is neutralised in plasma already
Hemagglutinogens
- RBC surface
- Production of blood-agglutinating-antibody
- Agglutinate RBCs with corresponding antigens
- Blood type systems:
- System X (2 antigens)
- System Z (3 antigens)
Antigens found on the surface of RBCs are varieties of…
- Glycoproteids
- Glycolipids
Artificial hemagglutinins
- Antibodies form after immunisation
- Immunisation can be natural or artificial
Heterohemagglutinins
Agglutinate RBCs of other species
Isohemagglutinins
Agglutinate RBCs of the same species
Prevelance of Hemagglutinins
- Early immunisation (postnatally)
- Not present in newborns
- Concentration of antibodies is constantly growing
- Antibodies may disappear in the elderly
Give the two ways the RBC surface and plasma antibodies react
- Agglutination (More common in humans)
- Hemolysis (More common in animals)
Forms of incompatibility
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Biochemical polymorphism
- Structurally different to blood group antigens
- Complete the same function
- E.g Cattle transferrin polymorphism
Describe cattle transferrin polymorphism
- 6 serums seperated on agarose gel
- belong to cows of different genotypes
- Transferrin shows a different pattern in the individuals (after seperation)
- They’re allotted into types A-E
- Genetic differences observed between proteins
- These differences are linked to production traits
- Used in animal husbandry
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H-antigen forms the basic structure of which blood system?
- AB0
- Common in all humans
- Therefore no antibodies are formed against it
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If there is no AB0 blood group, it is refered to as…
Bombay-group
Blood groups A, B, AB and O are formed by…
- Further blood-type systems as wells as AB0
- If there are no additional groups synthesised
- → O group is default
What forms the A blood group antigen
N-acetyl-galactose-amine transferase enzyme
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How is blood group O generated?
- 0-gene
- Supresses production of:
- N-acetyl-galactose amine transferase
- N-acetyl-galactosyl transferase
- No A or B blood group is formed
What forms the B blood group antigen?
N-acetyl-galactosyl transferase
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IgM type antibodies
- Varieties of Hemagglutinine
- Prevent AB0 antigens entering the blood stream after birth
- if certain antigens not already present on RBCs
- Incompatability:
- Agglutination of RBCs by the serum
- Hemolysis
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AB0 blood type reactions
- Determining of an unknown blood group
- via agglutination
- RBCs react with a serum containing specific antibodies
- E.g Anti-A, Anti-B
- Incompatibility observed, determining RBCs antigen type
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Rh blood group - 1st pregancy
- Rh negative mothers can be immunised by her foetus’ Rh positive RBCs
- The formed antibody isn’t IgM-type, but IgG-type
- Crosses easier accross the placenta
- via micro-injuries during delivery
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Rh blood group - 2nd pregnancy
- Small amount of RBCs enter mother’s immune system
- Stimulating anti-Rh antibodies
- These dissolve foetal RBCs
- Leads to erythroblastosis foetalis
- Jaundice
- Death of foetus
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Rh-incompatibility
- Rh negative recipent gets RBCs from Rh positive donor
- Recipient is immunised
- IgG antibodies dissolve recipients RBCs
- Second inappropriate blood transfusion can cause significant damage
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Highest blood type in europid race
0 (45% prevelance)
Highest blood type in negrid race
0 (51% prevelance)
Highest blood type in mongoloid race
A (38% prevelance)
How do animal blood groups differ to humans?
In animals:
- No naturally formed antibodies against RBC-antigens of other individuals
- Blood type antigens appear in the plasma too
- Artificial antibody has hemolysing and not agglutinating character
Monovalent antibody
Specific against only a single antigen
RFLP
Restriction fragment length polymorphism
identifies individual DNA fingerprints
Describe the production of an antibody which only reacts with the C-blood type antigen
(With no specific antigen against the single C-group)
- Immunise animal2 with animal1’s washed RBCs (A,B,C antigens)
- Animal2: only anti-B and anti-C is produced
- Washing with B RBC-s, Anti-B is removed
- Monovalent Anti-C serum remains
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Number of blood group systems and antigen group factors in cattle
- 13 Blood group systems
- Approx. 100 group factors
Number of blood group systems and antigen group factors in sheep
- 8 blood group systems
- Approx 80 group factors
Number of blood group systems and antigen group factors in equine
- 8 blood group systems
- Approx 20 group factors
Number of blood group systems and antigen group factors in swine
- 15 blood group systems
- Approx 50 group factors
Number of blood group systems and antigen group factors in Dogs
- 12 blood group systems
- 13 group factors
Number of blood group systems and antigen group factors in cats
- 1 blood group system
- 2 group factors
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Similarities of antigens in two of the the blood type systems
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Chimeras
Individuals (once dizygotes) that during the foetal phase:
- The hemopoietic progenitor cell migrated from one fetus to another
- RBCs produced with the antigen structure similar to the original individual
This results in the same RBC and WBC antigen structure
How are chimeras identified?
Where one twin is positive and the other is negative
Freemartinism
- Sterile female who was twins with a male
- Testosterone of the male twin inhibits the formation of the fertile female
- 10% chance of the female being fertile in the situation of being a twin to a male
- Can be selected by blood type examination
- Detection of XY type chromosomes
- Economically viable during animal husbandry
Give an example of blood group production traits in cattle
- B-system blood type
- Production of milk lipids
Give an example of blood group production traits in swine
- H blood type, PHI gene
- Meat quality and stress sensitivity
Give an example of blood group production traits in sheep
- 0 blood type, L antigen
- Serum phosphatase level and low RBC potassium level
Meat from a stress sensitive swine produces…
Large amounts of exsudate after cutting
lower market and nutritional value
Blood transfusion
- Substitution of lost RBCs
- Assures gas transport
Blood transfusion in large animals
Large animals:
- low antibodies - no consideration needed theoretically
- Small proportion transferred initially
- If no incompatibility, transfusion commences
Blood transfusion in small animals
- Three drops of:
- Donor blood cells
- Recipient’s plasma
- Physiological NaCl solution
- Check for hemolysis or agglutination
- Transfusion can be completed if none present
Blood transfusion in cats
- In life-saving situations:
- Blood of a donor dog can be transfused
- Not used anymore
- Blood typing kits now available
When can cat blood be donated to another cat?
After completing cross reaction tests
When can dog blood be donated to another dog?
After completing cross reaction tests
When can dog blood be donated to a cat?
In case of emergency without testing
Blood cell survival after transfusion of totally compatible donor and recipient
Normal lifetime (120 days)
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(Figure: A)
Fate of blood cells after a partly compatible blood transfusion
- Significant hemolysis
- Enough supply for 5-10 days of normal gas transport
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(Figure: B)
Blood cell survival after transfusion of totally incompatible donor and recipient
- Damage is caused
- Each RBC hemolyses immediately
(Figure: C)
Hemolytic illnesses of the newborn Horse
- Rh-like antigens
- Problem formed only postnatally
- Epitheliochorial placenta (barely in endometrium)
- Immunoglobulins absorbed from colostrum within 36 hours
- Symptoms:
- Hemolysis
- Neonatal jaundice
- Solution:
- Nursing the newborn
Hemolytic illnesses of the newborn swine
- Rh-like antigens
- Postnatal problem
- Swine antigen might cause incompatibility
- Epitheliochorial placenta (barely in endometrium)
- Immunoglobulins absorbed from the colostrum
- Symptoms:
- Hemolysis
- Neonatal jaundice
- Solution:
- Nursing the newborn
Hemostasis
- Blood clotting
- Defense reaction preventing loss of blood
- Vascular reaction
- Aggregation of platelets
- RBCs containing red thrombus forms
- Held in place by fibrin fibres
How is pathological clot formation prevented in the body?
A balance of:
- Hemostasis
- Self-inhibiting mechanism
The lack of blood coagulation
Hemophylia
Physiological micro-injuries
- Number is more significant
- Occurs constantly in all tissues
- Hemostasis is important in the ability to immediately repair these bleeds
Hemostasis balance system
If something causes bleeding or coagulation and it prevails for a longer period, it has pathologic consequences
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Imbalance of the hemostasis system
- Decreased healing
- hemophilia, bleeding sickness
- Increased clot forming mechanisms +
- Pathologically decreased clot removal
- Thrombosis, pathological clot forming
Summary of the hemostasis reaction
- Injury
- Vascular reaction
- Thrombocyte reaction
- Coagulation cascade mechanism
- Fibrinogen-fibrin transformation
- Red/white thrombus formation
- Blood loss stops
- Decreased vascular reaction
- Cascade inactivates
- Fibrinolysis
- Thrombolysis
- Vessel wall repair
- Complete healing
Vascular reaction
- Contraction after injury
- Depolarisation of smooth muscle cells
- Tissue vasoconstrictor factors
- Causes platelet formation
- Drop in perfusion
- Platelet aggreagtion
How are platelets attracted to injured endothelial cells
Binding to negative charges of injured endothelial areas
(Primary aggregation)
How does von Willebrand factor assist the thrombocyte reaction?
- Connects the injured surface with the thrombocytes
- Aggregation increases
Summarise the thrombocyte reaction
- Intima injury
- Primary activation
- Platelet binds to exposed collagen
- Von willebrand factor increases primary activation
- Secondary activation starts
- Thrombocytes bind together
- Secrete coagulation factors
- Endothelial PGI2 and NO production stops
- Thrombocyte secretion
- Thrombin forming activates
- Thrombocyte releases:
- Serotonin, ADP, PF-3, TXA
- White thrombus
Summarise the central ‘cascade’
- External/internal injury
- Xth coagulation factor → Xa factor
- Prothrombin → Thrombin
- Fibrinogen → IA loose fibrin net
- Fibrine net stabilises
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Roles of thrombin
- Enzyme
- Clot coagulation
- Clot elimination
- Self activating
- Coagulation-anticoagulation mechanisms
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Extrinsic way of coagulation
- External tissue injuries
- Inactive factor VII → Activated when plasma enters tissues
- Factor VIIa → Activates the factor X in the central ‘cascade’
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Intrinsic way of coagulation
- Plasma factor XII connects to the surface
- This binds kininogen
- Activating the enzyme kallikrein
- Transforms factor VII to active XIIa
- Activating the enzyme kallikrein
- XIIa = XI → XIa → activator complex
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Stopping blood coagulation: anticoagulation
- Anticoagulation
- Endothelial cells bind thrombin
- Thrombin activates protein-C
- Protein-C prevents activation of enzymes needed for intrinsic and extrinsic activation
Stopping blood coagulation: Fibrinolysis
- Thrombin stimulates plasminogen activation
- The produced plasmin is an enzyme which dissolves the fibrin net
Stopping blood coagulation: thrombolysis
- Phagocytosis decreases the size of the thrombus
- Increasing perfusion helps demolish the thrombus
Coagulation factor: I fibrinogen
Elementary substance of the stable fibrin net
Coagulation factor: II Prothrombin
Central enzyme: Clot forming and elimination
Coagulation factor: III Tissue factor
Initiator of the extrinsic way
Coagulation factor: IV calcium ion
Fixes and activates the members of the cascade
Coagulation factor: V proaccelerin
A member of the central activator complex
Coagulation factor: VI
Not in use anymore
Coagulation factor: VII proconvertin
Initiator of the extrinsic way
Coagulation factor: VIII Antihaemophilic factor A
Member of the intrinsic activator complex
Coagulation factor: IX Christmas factor
Member of the intrinsic way
Coagulation factor: X Stuart-prower factor
Integrator of the intrinsic and extrinsic ways
Coagulation factor: XI plasma thromboplastin antecedent
Secondary initiator of the intrinsic way
Coagulation factor: XII Hageman factor - contact factor
Primary activator of the intrinsic way
Coagulation factor: XIII Lóránd-Laki, Fibrin stabilising factor function
Forms a fibrin-polymer from monomers
Coagulation factor: Kininogen
Activates factor VII and kallikrein
Coagulation factor: Kallikrein
Activates factor XII
The role of vitamin K
- Calcium-binding gama-carboxyl-glutamic acid on the end of factors II, VII, IX, X and tissue factor GIa-proteins
- Coenzyme of the carboxylation of the glutamic acid in the liver is reduced vitamin K
Practical significance of vitamin K
- Natural intoxications
- Dicumarol
- Antagonises warfarin
- Inhibits coagulation
- Prevents thrombus formation
- During surgical interventions
- Cardiac valve etc.
- During surgical interventions